Study points to new breast cancer-susceptibility gene

Feb 08, 2007

A gene whose existence was detected only a couple of years ago may increase women’s risk of breast cancer when inherited in a mutated form, and may contribute to prostate cancer as well, researchers at Dana-Farber Cancer Institute and colleagues in Finland report in a new study.

The gene, known as PALB2, may play a role in only about 1 percent of breast cancer cases in the select population that was studied (Finnish women), but its discovery sheds light on the complex web of gene interactions that underlies the disease, say the authors of the study, which is being published by the journal Nature on its Web site and later in a print edition.

"Breast cancer can arise from a wide variety of genetic abnormalities, and mutations acquired during the evolution of breast tumor cells are relatively common in the disease," said the study’s co-lead author, Bing Xia, PhD, of Dana-Farber. "However, only about 10 percent of all cases are the result of inherited mutations, and, of those, only about 20-30 percent result from mutations in the two main breast cancer-susceptibility genes, BRCA1 and BRCA2. So there is room for other such genes to be discovered."

The new study stems from research by Xia and Dana-Farber's David Livingston, MD, a senior author of the paper, into BRCA2's "binding partners" – proteins that interact with the BRCA2 protein. They found that the PALB2 protein is an especially close partner of BRCA2, with substantial portions of the proteins binding to each other.

"We found that PALB2 helps anchor BRCA2 in key areas of the cell nucleus, where BRCA2 repairs damaged DNA," Xia said. Mutations in BRCA2 can prevent such repairs from being made, which can lead to runaway cell growth. If BRCA2 is normal, but PALB2 is defective, BRCA2 may be out of position for fixing damaged DNA, with similar pathological effects on cell growth.

To determine whether PALB2 mutations are implicated in both hereditary and sporadic breast cancer, researchers at Oulu University Hospital in Finland screened tissue from 113 Finnish families with a history of the disease. Three of the families were found to have the same mutation of the gene.

The Finnish team next screened tissue from 1,918 breast cancer patients, some of whom had inherited cancer-susceptibility genes, some of whom had not. Eighteen patients – or about 1 percent of the entire group – were found to carry the same PALB2 mutation; and most of them turned out to have a family pattern of the disease.

"The mutation causes the middle portion of the PALB2 protein to be truncated," Xia remarked. "That seems to hinder its ability to bind to BRCA2, which, in turn, hinders DNA repair. The screening result suggests that carrying the mutation increases one’s risk of breast cancer approximately four fold."

The Finnish researchers also screened tissue from 141 male breast cancer patients, 476 colorectal cancer patients, and 639 prostate cancer patients. In one family where prostate cancer had occurred in several generations, every family member with prostate cancer whom it was possible to test was found to carry the PALB2 mutation, suggesting that the gene plays a role in this form of cancer as well. The mutation did not turn up in male breast and colorectal cancer patients, however.

"Our research suggests that mutations in PALB2 can be an influential factor in breast cancer development, like those affecting BRCA2," Xia observed. "But since we suspect that such mutations occur less frequently in PALB2 than BRCA2, they are not responsible for as many breast cancer cases as BRCA2 mutations."

Xia added that the discovery of a PALB2 mutational link to breast cancer "may well increase one’s ability to identify women at elevated risk for the disease and to devise appropriate prevention and, possibly, treatment strategies, as well."

For the first time, researchers at the University of California, Davis, have watched single strands of DNA being prepped for repair. The research, published this week in the journal Nature, has implications for understanding the or ...

An international study led by researchers at Memorial Sloan-Kettering Cancer Center has identified genetic variants in women with BRCA2 mutations that may increase or decrease their risk of developing breast cancer. The study ...

(PhysOrg.com) -- A new study from UC Davis shows how, like a conjuring trick with interlocking rings, two interlocked pieces of DNA are separated after DNA is copied or repaired. The finding was published online Oct. 10 in ...

Kelly Metcalfe, a professor at the Bloomberg Faculty of Nursing, focuses her research on a unique population of women faced with some really tough decisions and helps them reach satisfactory conclusions.

After five years of follow-up, a majority of asymptomatic, benign thyroid nodules exhibited no significant change in size, or actually decreased in size, and diagnoses of thyroid cancer were rare, according to a study in ...

Tumor recurrence following a period of remission is the main cause of death in cancer. The ability of cancer cells to remain dormant during and following therapy, only to be reactivated at a later time, frequently ...

Extra virgin olive oil (EVOO), long-known for its heart health benefits, has now been identified for its rapid destruction of cancer cells. While scientists have proven that the oleocanthal compound found ...

A magnetic resonance spectroscopy (MRS) technique that monitors biochemical changes in tissue could improve the management of women at risk of breast cancer, according to a new study published online in the ...

Despite sharp increases in spending on cancer treatment, cancer mortality rates in the United States have decreased only modestly since 1970, Samir Soneji, PhD of Dartmouth's Norris Cotton Cancer Center and The Dartmouth ...

User comments : 0

Please sign in to add a comment.
Registration is free, and takes less than a minute.
Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.

Javascript is currently disabled in your web browser. For full site functionality, it is necessary to enable Javascript.
In order to enable it, please see these instructions.